The information contained in protein amino acid sequences has illuminated much of molecular biology. The Edman sequential degradation is the principal method by which almost all of these have been determined. The application of the Edman degradation to the sequencing of complete unfragmented proteins has been limited by incomplete understanding of its chemistry. The most severe problems are: (1) a general blocking reaction which significantly lowers the amount of sequencable peptide at each cycle; and (2) random chain splitting, where the peptide chain behaves as if it were broken in a random fashion. These two and other parameters such as incomplete coupling, incomplete cleavage, wash out and special blocking reactions, limit the number of effective cycles. The variables which affect the magnitude of the above parameters include type of isothiocyanate, temperature, pH, solvent, cleavage reagent and redox conditions. Quantitative investigations of these variables will make it possible to resolve the parameters and permit their optimization. Significantly diminishing only one of the two major problems will extend sequencing range to about 150 cycles; significant improvement in both problems will make it possible to sequence even much longer proteins. We will construct devices that support the chemical investigation and are capable of employing the optimal chemistry. A sequencer coupled with a quantitative identifier, both having a cycle time of about ten minutes, will help generate the large amount of data needed.